Search PubMed⌕ Search

Biomedical subjects

L Michel

Publications and source records attributed to L Michel.

At least 91 records · Page 5Linked to original sources
PubMed1988

Biosynthesis of paf-acether factor-acether by human skin fibroblasts in vitro.

The synthesis and release of paf-acether by fibroblasts from normal human skin was investigated in vitro. When fibroblasts in suspension (1 X 10(6) cells) were stimulated with 2 microM Ca1+ ionophore A23187 (Io), they synthesized a material that aggregated aspirin-treated washed rabbit platelets and was identified as paf because 1) the platelet aggregation it induced was inhibited by BN 52021, an antagonist of paf putative receptors; 2) the factor was inactivated by phospholipase A2 but was insensitive to lipase from Rhizopus arrhizus; 3) it exhibited the same retention time as synthetic paf during standard and reverse phase HPLC elution. Paf production by fibroblasts occurred as soon as the first min of Io stimulation (287 +/- 92 pg/1 X 10(6) cells), reached a maximum at 5 min (369 +/- 85 pg/1 X 10(6) cells) and decreased thereafter. Half of the fibroblast-produced paf was recovered in supernatants. Addition of exogenous 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-paf) at 0.1 microM and/or acetyl-coenzyme A at 0.1 mM to fibroblasts during Io stimulation enhanced paf production by two- and three-fold, respectively. The paf precursors, i.e., 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (1-alkyl-2-acyl-GPC) and lyso-paf, were detected in fibroblasts either stimulated with Io or not. These precursors exhibited 80% hexadecyl and 20% octadecyl chains at the sn-1 position of the molecules, as determined by reverse phase HPLC and gas chromatography analysis. The present results are the first to demonstrate the synthesis and release of paf by fibroblasts from normal human skin. Such production within the dermis might account for the development of cutaneous inflammation and for the pathogenesis of many skin disorders.

Adult↗
PubMed1988

Inhibitory effect of oral cetirizine on in vivo antigen-induced histamine and PAF-acether release and eosinophil recruitment in human skin.

The use of a noninvasive skin chamber technique in vivo in pollen-sensitive patients allowed us to quantify the time-course release of histamine and the recruitment of inflammatory cells (i.e., neutrophils, monocytes, and eosinophils) in skin sites challenged with pollen, histamine, and compound 48/80. The new H1-receptor antagonist, cetirizine 2 HCl, orally administered with 10 mg once a day to pollen-sensitive patients in a double-blind, crossover study versus placebo, induced a significant decrease in the wheal-and-flare cutaneous reaction induced by intradermal injection of pollen, histamine, and compound 48/80. It also significantly inhibited the immediate histamine release occurring in skin chambers after pollen introduction, whereas it did not significantly inhibit the late release. In patients receiving placebo, we detected platelet-activating factor-acether in media collected at the sixth hour from chambers filled with pollen. With cetirizine 2 HCl treatment, platelet-activating factor-acether was not detected in chamber media. Interestingly, cetirizine 2 HCl significantly reduced the eosinophil recruitment observed on the superficial dermis 24 hours after pollen challenge.

Administration, Oral↗
PubMed1988

Inhibition of H+-transporting ATPase by formation of a tight nucleoside diphosphate-fluoroaluminate complex at the catalytic site.

Inhibition of the mitochondrial and bacterial F1-type ATPases [of ATP phosphohydrolase (H+-transporting), EC 3.6.1.34] by fluoride was found to depend on the presence of aluminum and ADP at the catalytic site(s) of F1-type ATPase. AIF-4 was demonstrated to be the active fluoroaluminate species. The identical pattern of inhibition of F1-type ATPase activity obtained in the presence of ADP and NaF with beryllium, a metal that forms fluoride complexes strictly tetracoordinated, suggests that aluminum acts through a tetrahedral complex. Inhibition of isolated F1-type ATPase by AIF-4 in the presence of ADP cannot be reversed by ADP, ATP, or chelators of aluminum. However, the inhibition of the ATPase activity of the F1 sector in submitochondrial particles caused by AIF-4 and ADP was reversed upon addition of an oxidizable substrate. Uncouplers prevented the reversal of inhibition, suggesting that the protonmotive force generated by respiration was responsible for the relief of inhibition. Because of structural similarities between AIF4- and , AIF4- is postulated to mimic the phosphate group of ATP and form an abortive complex with ADP at the active site(s) of F1-type ATPase.

Adenosine Diphosphate↗
PubMed1988

Characterization of specific leukotriene C4 binding sites on cultured human keratinocytes.

Peptidoleukotriene C4 (LTC4) and leukotriene B4 (LTB4) are both suspected of being inflammatory mediators and epidermal mitogenic agents in cutaneous psoriatic lesions. In the present study an LTC4 specific binding site was characterized in membranes from cultured human keratinocytes (Kd, 8.7 nmol/l; Bmax, 1.2 pmol/mg protein). In contrast LTB4 did not show any high affinity binding which could account for its biological effects. These data suggest that LTC4, unlike LTB4, acts on epidermal cells through a receptor-mediated mechanism.

Binding Sites↗
PubMed1988

Prostaglandin D2 generation in mouse bone marrow-derived mast cells exposed to dexamethasone is associated with endogenous peroxidase activity.

The appearance of fixative-sensitive peroxidase activity in the nuclear envelope and endoplasmic reticulum of bone marrow-derived mast cells (BMMC) cultured in the presence of 1 microM dexamethasone (DM) for up to 14 days and its relationship with immunologic release of prostaglandin D2 (PGD2) by these cells were studied. Endogenous peroxidase activity, previously shown as a marker of arachidonic acid metabolism in various cell types, was visualized by cell incubation in 3,3' diaminobenzidine-containing solution before glutaraldehyde fixation. PGD2 release was induced by passive sensitization of BMMC with an optimal dose of monoclonal IgE and subsequent challenge with specific a antigen. We found that 4-week-old BMMC, used as the starting population of the present study, exhibited immature morphologic features, did not present peroxidase activity when cytochemically processed, and released minute amounts of PGD2 in response to IgE-dependent stimulation. When such BMMC were exposed to DM during 24 hours, they showed aldehyde-inhibited peroxidase activity in the perinuclear envelope and a few endoplasmic reticulum segments. As compared with untreated cells, 24-hour DM-exposed BMMC released higher amounts of PGD2 upon immunologic stimulation. After an additional 14-day period of DM exposure, an intense peroxidase activity was detected in the perinuclear envelope and the endoplasmic reticulum of BMMC, which, under immunologic stimulation, released as much as 42.4 +/- 14.7 ng of PGD2/1 x 10(6) cells. Aminotriazole (20 and 50 mM) extinguished both peroxidase activity and PGD2 release from BMMC whereas indomethacin (1 microM) suppressed PGD2 production, but did not alter endogenous peroxidase activity. Previous cell fixation with glutaraldehyde totally inhibited endogenous peroxidase reaction in DM-exposed BMMC. Moreover, 14-day DM-exposed BMMC exhibited morphologic characteristics of mature mast cells and possessed alcian blue+/safranin+ granules. Therefore, the present data suggest that appearance of peroxidase activity in the nuclear envelope and the endoplasmic reticulum of DM-exposed BMMC is associated with the ability of the cells to synthetize PGD2 and appears as a cytochemical marker of the in vitro maturation of mouse bone marrow-derived mast cells.

Aldehydes↗
PubMed1987

Biologic properties of LTB4 and paf-acether in vivo in human skin.

Using an improved skin chamber technique, the consequences of prolonged contact of leukotriene B4 (LTB4) and platelet-activating factor (paf-acether) with human dermis were evaluated quantitatively and kinetically in vivo. Leukocyte chemotaxis, histoenzymologic alterations, and modifications in vascular permeability were studied in two sets of experiments. In a first set of experiments, the dose-effect relationship of LTB4 and paf-acether on leukocyte migration was studied. LTB4 (3 X 10(-8) M to 9 X 10(-7) M) in Hanks' balanced salt solution (HBSS) elicited an intense dose-dependent and time-dependent neutrophil migration. Paf-acether, at the same concentration range, induced a significant increase in cell migration only at 9 X 10(-7) M and when diluted in HBSS containing 0.25% serum albumin (HBSS-BSA). Histoenzymologic analysis demonstrated that LTB4 in vivo induced degranulation of most of the neutrophils migrating through the dermis. Paf-acether caused mild degranulation of neutrophils and induced the appearance of degranulated basophils in dermal vessels. A second set of experiments was designed to study simultaneously the modifications in vascular permeability and cell migration induced by LTB4 and paf-acether, with or without prostaglandin E2 (both at a concentration of 3 X 10(-7) M in HBSS). Since spontaneous protein diffusion in HBSS progressively declined up to a plateau reached after 20 h (1.2 +/- 0.15 mg of proteins/cm2/2 h), these experiments were carried out after a 20-h equilibration period. Leukotriene B4 induced a late and slight increase in vascular permeability. Paf-acether did so intensely and transiently. Prostaglandin E2 significantly enhanced protein diffusion and neutrophil migration induced by LTB4 and, to a lesser extent, by paf-acether. Interestingly, despite the reintroduction into the skin chambers of freshly prepared solutions containing the mediators, leukocyte migration and protein diffusion progressively decreased during the experiments. This suggests the local production of anti-inflammatory factors that inhibit local mediators and thus regulate the inflammatory response.

Capillary Permeability↗
PubMed1987

Binocular visual acuity of neonates: the acuity card procedure.

The acuity card procedure is a variant of the forced-choice preferential looking technique. In this study, four observers each tested 10 infants (all healthy fullterm neonates) with acuity cards containing either a one-aperture or a two-aperture stimulus configuration. For both card types the mean test time was eight minutes. No effect on acuity results was found between the two different configurations. The mean acuity values were within one octave of those reported in most previous behavioral studies of the acuity of neonates. The authors consider that the acuity card procedure provides a rapid, accurate technique for assessment of healthy newborn infants in a hospital setting.

Fixation, Ocular↗
PubMed1987

[Psychotherapy and culture].

This is a follow-up study of a group of patients of Foreign origin for which an indication for analytic psychotherapy was found. The importance of mutual therapist-patient recognition is emphasized. It seems necessary that the patient masters the cultural and socio-economic environment in which he lives, in order to open himself up to an intra-psychic reality. Finally, we formulate the hypothesis that symptoms shown by the patient reveal indirectly adjustment disorders to the cultural environment.

Acculturation↗
PubMed1987

Cryoanalgesia for post-thoracotomy pain relief.

A randomized study comparing the postoperative requirements of narcotics of three groups of patients (Group I: no analgesia; Group II: internal intercostal nerve block; Group III: cryoanalgesia) was conducted. This study was performed in order to assess the efficiency of cryoanalgesia versus internal intercostal nerve block to obtain pain relief after thoracotomy. Regarding post-operative narcotic requirements (Piritramide-Dipidolor), there was no significant difference between Group I and Group II patients, but patients from Group III required a significantly lower amount of narcotics during the first 36 postoperative hours (p less than 0.01). We conclude that, although cryoanalgesia does not provide complete post-thoracotomy pain relief, it is however an easy and safe method and is more efficient than internal intercostal nerve block for pain relief after thoracotomy.

Adult↗
PubMed1987

Interaction of a benzomorphan opiate with acetylcholinesterase and the nicotinic acetylcholine receptor.

The benzomorphan opiate, (-)N-allynormetazocine [(-)ANMC, (-)SKF10047], has been shown previously to bind two distinct sites on acetylcholine receptor (AChR)-rich membranes from Torpedo electroplaque. The low affinity site seems to correspond to the site for noncompetitive blockers on the AChR. The high affinity site, which can be photoaffinity labeled using UV irradiation, was distinct from this site. We show here, using a variety of techniques, that the high affinity binding site for (-)ANMC is on the acetylcholinesterase (AChE) associated with these membranes. The Triton X-100-solubilized peptide photolabeled with (-)[3H]ANMC co-migrates with acetylcholinesterase activity on velocity sucrose gradient centrifugation and fast protein liquid chromatography. In addition, the labeled peptide cannot be precipitated with monoclonal or polyclonal antibodies raised against the nicotinic AChR but can be precipitated with anti-AChE antibodies. Localization of the binding site on AChE was confirmed by photolabeling of and reversible binding to the 11 S AChE purified from Torpedo californica. The binding and photolabeling had characteristics and affinity similar to those for the high affinity binding site in Torpedo electroplaque membranes. Competition studies with specific AChE inhibitors suggest that the binding site may be the catalytic site of the enzyme, which exists on the 66-kDa globular protein. The effect of (-) and (+)ANMC on AChE activity was also investigated. ANMC inhibited AChE activity at micromolar concentrations in a stereoselective fashion, with the (-)isomer exhibiting a 2-fold higher affinity than the (+) isomer. The inhibition was consistent with a competitive blockade of AChE activity.

Acetylcholinesterase↗
PubMed1986

Mechanism of binding of a benzomorphan opiate to the acetylcholine receptor from Torpedo electroplaque.

The mechanism of binding of the benzomorphan opiate, (-)-N-allylnormetazocine [(-)-ANMC], to Torpedo acetylcholine receptor (AcChR)-rich membranes was investigated. Using a centrifugation assay, two equilibrium binding affinities were observed with KD values of 0.4 and 2 microM. The KD and the apparent Bmax of the higher affinity component were decreased by cholinergic agonists and antagonists but not by alpha-bungarotoxin alone. The high affinity binding site (KD = 0.4 microM) was found to be distinct from the binding site for tetracaine, a noncompetitive blocker. The apparent association rate constant was essentially independent of receptor concentration both in the presence and absence of the cholinergic agonist, carbamoylcholine. When carbamoylcholine was equilibrated with the AcChR prior to (-)-[3H]ANMC addition, the association rate constant was 2- to 3-fold greater than in the absence of cholinergic effectors. When carbamoylcholine and (-)-[3H]ANMC were added simultaneously to AcChR-rich membranes, association was too rapid to resolve manually and binding measured at 5 sec was greater than the equilibrium level both in the presence and absence of carbamoylcholine. Binding decreased as a function of time, reaching its equilibrium level with a time constant of approximately 1 min. This effect appeared to be agonist specific since it was not observed when the antagonist, d-tubocurarine, replaced carbamoylcholine. In the absence of cholinergic ligands, dissociation of (-)-ANMC was biphasic (t1/2 values of less than 5 sec and approximately 2.5 min) and, in the presence of cholinergic ligands, was monophasic (t1/2 of 40 sec). The simultaneous addition of carbamoylcholine and (-)-[3H]ANMC to the membranes initially results in a biphasic dissociation (t1/2 of 5 and 30 sec) which becomes monophasic with increasing times of incubation. A mechanism is proposed involving an isomerization of the receptor-ligand complex which agrees quantitatively and qualitatively with the data.

Affinity Labels↗